Generation and containerization of radioisotopes



May 27, 1969 G. OGIER ET AL 3,446,965 GENERATION AND CONTAINERIZATION OF RADIOISOTOPES Filed Aug. 10, 1966 Sheet of 2 FIG.|.

May 27, 1969 G. OGIER ET AL GENERATION AND CONTAINERIZATION OF RADIOISOTOPES Sheet Q 5 m P 47 f /Z Filed Aug. 10, 1966 F IG. 2.

United States Patent US. Cl. 250-106 15 Claims ABSTRACT OF THE DISCLOSURE Apparatus and method for generating a sterile daughter radioisotope solution from a generator charged with a parent radioisotope and containerizing the daughter radioisotope in an evacuated container. The apparatus includes a shield having an upper chamber for receiving the generator and a lower compartment for receiving an evacuated container and a containerization unit. The shield is provided with a door for insertion and removal of the container and containerization unit. The containerization unit contains a transfer vessel for receiving the eluate containing the dissolved radioisotope, the vessel having a tubular needle extending therefrom adapted to be pierced through a stopper in the evacuated container for suction of the eluate from the vessel into the evacuated container. The vessel is supported in the lower compartment above the container, the vessel and container being adapted for relative vertical movement to cause the needle to pierce the stopper for suction of the eluate from the vessel into the container.

' This invention relates to the generation and containerization of radioactive isotope solutions, and more particularly to the sterile containerization of such solutions obtained as the eluate from an isotope generator.

This invention is particularly concerned with the preparation and containerization under sterile conditions of a solution of a daughter radioisotope such as technetium-99m generated from a parent radioisotope such as molybdenum-99. Conventionally, the preparation of a daughter radioisotope from a parent radioisotope has been carried out using a so-called generator containing the parent radioisotope and an anion exchange medium or other medium such as alumina having a high adsorption capacity for the parent radioisotope but a low adsorption capacity for the daughter radioisotope. The desired daughter radioisotope is eluted by washing with a suitable solvent or eluting solution such as a sterile, pyrogen-free, isotonic saline solution. The resulting solution containing the daughter radioisotope in the form of a dissolved salt is useful as a therapeutic agent or in medical diagnosis, for example, and is adapted for intravenous or oral administration.

The generator containing the parent radioisotope, adsorption medium and daughter radioisotope is frequently referred to in the art as a cow and the elution of the daughter radioisotope therefrom is generally referred to in the art as milking the cow.

Some Widely used daughter radioisotopes have relatively short half-lives, and it is important therefore that the radioisotope be generated or prepared in the hospital, clinic or other place of use shortly before usage. While satisfactory generators or cows have been available heretofore, the preparation of daughter radioisotopes therefrom has nevertheless presented problems since it is necessary for the user to maintain a shielded work space in which to carry out the generation or milking process. In some instances, this problem has been met by establishing in a separate room the requisite facilities for avoiding contamination and reducing radiation exposure to personnel, but such facilities are costly to install. Also, it is necessary to generate and containerize the desired radioisotope in such a manner as to provide a sterile solution ready for intravenous use, and this has heretofore required the institution of special procedures.

Therefore, among the several objects of the invention may be noted the provision of an improved method and apparatus for generating and collecting a solution of a daughter radioactive isotope; the provision of such a method and apparatus which produce a solution of a daughter radioactive isotope in a sterile condition ready for usage; the provision of a method and apparatus of this character which satisfy radiation safety requirements; the provision of such a method and apparatus which minimize operator handling and exposure; and the provision of a method and apparatus of the type indicated which are simple, reliable and economical to use. Other objects and features will be in part apparent and in part pointed out hereinafter.

The invention accordingly comprises the constructions and methods hereinafter described, the scope of the invention being indicated in the following claims.

In the accompanying drawings, in which one of various possible embodiments of the invention is illustrated,

FIG. 1 is a view in elevation of a shield constituting part of the apparatus of this invention;

FIG. 2 is a vertical section through the shield, on a larger scale than FIG. 1, showing a generator and a containerization unit of the apparatus in place in the shield;

FIGS. 3, 4 and 5 are horizontal sections taken, respectively, on lines 3-3, 4-4, and 55 of FIG. 2, all on a smaller scale than FIG. 2; and

FIG. 6 is a detail section taken on line 66 of FIG. 2.

Corresponding reference characters indicate corresponding parts throughout the several views of the drawings.

Referring to the drawings, there is indicated at 1 in FIGS. 2 and 3 a generator or cow for elution of a daughter radioisotope from a parent radioisotope. As shown, this generator comprises a sleeve 3, open at both ends, preferably made of transparent plastic, in which is mounted an elution cartridge 5. The latter comprises a glass barrel 7 open at its upper end and formed with a funnel 9 at its lower end. A fritted glass filter 11 is lodged in the barrel adjacent its lower end just above the funnel. Packed in the barrel on this filter is a charge 13 of the parent radioisotope adsorbed on an anion exchange medium,, alumina or other suitable medium having, under suitable conditions, a high adsorption capacity for the parent radioisotope but a low adsorption capacity for the daughter radioisotope. The charge is retained in the barrel by a screen 15 lodged in the barrel on top of the charge. For generation of technetium-99m, for example, the charge may comprise molybdenum-99, in the form of ammonium molybdate, as the parent radioisotope adsorbed on alumina, the latter constituting a medium having a high adsorption capacity for ammonium molybdate Mo-99 but a low adsorption capacity for the daughter technetium-99m compound in the presence of certain known eluting solutions.

The barrel 7 is of smaller diameter than the inside diameter of sleeve 3 and is concentrically mounted therein with an annular space 17 between the sleeve and barrel by means of spacers 19 suitably bonded to the sleeve and the barrel. The top of the barrel is generally flush with the top of the sleeve, and the tip of the funnel is somewhat above the lower end of the sleeve. The generator is adapted for elution (milking) to obtain the daughter radioisotope by pouring an eluant or eluting liquid, such as a sterile, pyrogen-free, saline solution, into the open upper end of the barrel 7, the eluting liquid passing through the screen and thence through the charge 13 for eluting the daughter radioisotope from the parent radioisotope, the resultant solution (the eluate or milk) containing the daughter radioisotope passing through the filter 11 and draining out through the funnel 9. In the case of technetium-99m, for example, the daughter radioisotope is present in the eluate as sodium pertechnetate.

For the elution of the daughter radioisotope from the generator 1, the latter is placed in a chamber 21 in the upper end of a shield 23, which is made of a dense shielding material such as lead bonded to a rigid material such as steel. The steel provides structural stability and the lead provides shielding for the technician carrying out the eluting operation from the radioactive emission of the charge 13 in the generator, and the radioactive emission of the collected eluate. This shield 23, as shown, comprises an elongate cylindric lead body, extending upward from a flat circular base 25, having a lower thin-walled section 27 surmounted by an upper thick-walled section 29. The lower thin-Walled section defines a relatively large compartment 31 for a containerization unit 33 and is provided with a door 35 for insertion of unit 33 in the compartment and removal of unit 33 from the compartment. The upper section 29 is cored out to provide the chamber 21 for the generator 1, this chamber being of elongate cylindric form extending down from the top of the shield and opening at 37 into the top of the compartment 31. This opening 37 is in an inwardly directed an nular flange 39 at the lower end of the chamber 31 which constitutes a seat for the lower end of the sleeve 3 of the generator 1.

The minimum thickness of shield sections 27 and 29 is determined by the energy of the radioactive emissions from the daughter and parent radioisotopes, respectively. For example, Mo-99 emits high energy radiation while the radiation from the daughter Tc-99m is much less energetic, hence, the relative thickness of sections 29 and 27 as illustrated and discussed.

The principles and methods of calculating the necessary shielding for any given parent-daughter pair are well known to those skilled in the art.

The thick-walled upper section 29 of the shield has a height somewhat greater than that of the generator 1 so that, when the generator is inserted in chamber 21 with the lower end of the sleeve 3 of the generator engaging the seat 39, the upper end of the generator is somewhat below the upper end of the shield. Chamber 21 has a counterbore 41 providing an annular recess around its upper end for reception of a lead closure 43 for the upper end of the chamber.

The containerization unit 33 provides for the sealed sterile containerization of the eluate flowing down out of the tunnel 9 in a sealed, sterile container 45. This container, as shown, in a glass bottle having a neck 47 sealed at its upper end by a stopper 49 which is adapted to be pierced by a needle. Stopper 49 is conventionally a rubber stopper, initially covered by foil 51, e.g., aluminum foil, having a portion adapted to be peeled away from the top of the stopper to expose the latter. The container or bottle 45, as initially supplied for the containerization operation, is evacuated of air. The containerization unit includes a transfer vessel 53 for receiving the eluate from the funnel 9 having a tubular needle 55 extending therefrom adapted to be pierced through the stopper 49 for suction of eluate from the vessel 53 into the evacuated sterile bottle 45. Means indicated generally at 57 is provided for supporting the vessel 53 in position above the bottle with the needle 55 extending downward from the vessel 53, with the lower end of the needle engaging the stopper 49, and with the vessel 53 and the bottle adapted for relative vertical movement to cause the needle to pierce the stopper for the suction of eluate from the vessel into the bottle.

Vessel 53, as shown, is an elongate cylindric vessel, which may be constituted by the barrel of a conventional syringe. It has a tip 59 on which is secured a holder 61 for a submicron filter 63 adapted to filter bacteria as well as any solids out of the eluate. This filter may be, for example, a 0.22 micron filter. The holder 61 for the submicron filter comprises a lower cup-shaped member 65, the filter being clamped in the bottom of this member by a plug 67 screw-threaded therein. The plug has a central inlet 69 which is pressed on the tip 59 of the vessel or syringe barrel 53, and the member 65 has a nipple 71 extending downward from the center of its bottom. The upper end of the tubular needle 55 is socketed in a plastic fitting 73 which is pressed on the nipple 69. A rubber plug 75 is provided for the tip of the needle.

The containerization unit 33, as shown, includes an open-topped receptacle 77 for holding the bottle 45 with the bottle inserted in a cup-shaped lead shield 79. Receptacle 77 is constituted by a transparent plastic cup which is somewhat taller than the bottle. It has a relatively thin circular bottom 81 and a relatively thick cylindric peripheral wall designated 83. The outside diameter of the lead shield or cup 79 is only slightly less than the inside diameter of the cylindric wall 83 of the receptacle 77 so that the lead cup has a loose but relatively close fit in the receptacle. The inside diameter of the lead cup 79 is only slightly greater than the outside diameter of the bottle so that the bottle has a loose but relatively close fit in the lead cup. The receptacle 77 is taller than the bottle and the lead cup.

The means 57 for supporting the syringe barrel 53 comprises a tubular cylindric housing 85 preferably made of a transparent plastic having the same outside diameter as the outside diameter of the cylindric wall 83 of the receptacle 77. The bore in housing 85 is designated 87. It extends down from the upper end of the housing to an inwardly directed annular flange 89 at the lower end of the housing, where there is a cylindric extension 91 having a close but lose fit in the upper end of the receptacle 77. Pins 93- projecting radially outward from extension 91 are adapted for entry in bayonet slots 95 formed in the cylindric wall of receptacle 77 for detachably locking the housing on the receptacle 77 These bayonet slots have vertical entrance ends 95a (see FIG. 6). The opening at the lower end of the housing bounded by flange 89 is designated 97. A cupped metal washer 99 constituting an annular guide is mounted on the upper end of the housing 85, this washer having an annular rim 101 bearing on top of the housing around the upper end of the bore 87, which is large enough loosely to receive the filter holder 67. The washer fits in the upper end of bore 87 and is thereby held in concentric relation with the housing 85. The assembly of the syringe barrel 53, filter holder 67 and needle 55 is loosely mounted in the housing with the upper end portion of the syringe barrel extending slidably through the opening 103 in the washer 99, the plug 75 at the lower end of the needle 55 engaging the bottle stopper 49, as shown in FIG. 2. The syringe barrel extends upward for some distance above the top of housing 85 and has laterally projecting ears 105 at its upper end. The overall height of the containerization unit 33 from the bottom of receptacle 77 to the upper end of the syringe barrel 53 is somewhat less than the height of compartment 31 in the shield 23. The base 25 of the latter has a shallow circular recess 107 for centering the receptacle 77 in the compartment 31, thereby centering the entire unit 33 in the compartment.

In the use of the above-described apparatus, generator 1 is inserted in chamber 21 from the top of the shield 23. Housing 85 is removed from the receptacle 77 to open the latter for insertion of the internal lead shield or cup 79 with an evacuated stoppered internally sterile bottle 45 in the cup 79. With the metal washer 99 removed from the housing 85, the syringe barrel 53 is inserted through the opening 103 in the washer, after which the filter holder 61 carrying the needle 55 is applied to the tip 59 of the syringe barrel. Then the syringe barrel with the filter holder and needle thereon is entered into the bore 87 of the housing from the upper end of the bore, the needle extending down through the opening 97 at the lower end of the housing. A sterile evacuated bottle 45 and the lead shield 79 therefor are inserted in the receptacle 77. The foil 51 is peeled away from the stopper 49, and the top of the latter is wiped with alcohol or a suitable sterilizing solution. The housing 85, carrying the syringe barrel 53 with the needle 55 extending downward from the filter holder 61 at the lower end of the barrel, is then positioned on top of the receptacle 77, with extension 91 entered in the upper end of the receptacle by locating of pins 93 in register with the vertical entrance ends 95a of the bayonet slots 95, after which the housing is rotated on its axis relative to the receptacle 77 to lock the housing on the receptacle via wedging down of the pins in the bayonet slots. As the housing is placed on the receptacle, the plug 75 on the lower end of the needle 55 engages the top of the bottle stopper 49, and the syringe barrel is thereby caused to rise to the elevated position with respect to the housing shown in FIG. 2 wherein the upper end of the syringe barrel is spaced upward from the upper end of the housing.

The entire containerization unit 33, assembled as above described, is then placed in compartment 31 of the shield 33 via the door 35 of the shield, and the receptacle 77 is seated in the recess 107 in the base of the shield This centers the unit 33 in the compartment. The door is closed, the requisite amount of eluting solution or eluant is poured into the barrel 7 of the generator 1, after which the closure 43 is applied. After all the eluant has passed through the charge 13 and the resultant eluate has been collected in the syringe barrel 53 (where it stays due to the closure of the lower end of the tubular needle by the rubber plug 75), the door 35 is opened, and the operator, reaching into the compartment 31, grasps the as sembly 85, 77 and thrusts it sharply upward. The ears 105 at the upper end of the syringe barrel 53 engage the bottom of the upper section 29 of the shield 21 to hold the barrel 53 and needle 55 from moving upward and the upward thrust of assembly 85, 77 carries the bottle 45 upward with the result that needle i caused to penetrate through the plug 75 and thence through the stopper 49. With the lower end of the needle 55 driven through the stopper, and with the existing vacuum in the bottle, the eluate is drawn from the syringe barrel 53 down through the filter 63 and the needle into the bottle. In passing through the filter 63, the eluate is freed of bacteria as well as any solids, and thus is bottled in sterile condition.

After the operation of drawing the eluate into the bottle has been completed, the containerization unit 33 is taken out of the shield 23, and the housing 85 i removed from the receptacle 77, resulting in the needle 55 being pulled out of the stopper 49, which immediately reseals itself. Then, the filled bottle 45 is taken out of the receptacle 77, ready for use. In case all of the eluate has not been drawn into the bottle, it is a simple matter to insert a syringe plunger into the syringe barrel 53, before removal of the housing and while the needle is still pierced through the stopper 49, and drive the plunger down to force the remaining eluate into the bottle.

It will be understood that the above apparatus may be used for preparation and sterile containerization of solutions of various daughter radioisotopes, especially those having relatively short half-lives, the preparation and containerization of technetium-99m. in the form of a solution of sodium pertechnetate from molybdenum-99 being only illustrative of the practice of the invention.

In View of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

As various changes could be made in the above constructions and methods without departing from the scope of the invention it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

What is claimed is:

1. The method of generating and containerizing a solution of a daughter radioisotope from a parent radioisotope comprising eluting the daughter radioisotope from a parent radioisotope and collecting the eluate by directing it into a receiver which has communication with a tubular outlet needle, and then driving the needle through a stopper of a sealed evacuated container for drawing the eluate from the receiver into the container.

2. The method of claim 1 wherein the container is internally sterile and the eluate collected in the receiver is filtered to render it sterile prior to its entry into the container.

3. Apparatus for eluting a daughter radioisotope from a generator charged with a parent radioisotope and containerizing the eluate in an evacuated container having a stopper at its upper end adapted to be pierced by a needle, comprising a shield having an upper chamber for receiving the generator and a lower compartment for receiving an evacuated container and a containerization unit,

said shield having a door for insertion and removal of said container and said unit,

said unit comprising a vessel for receiving the eluate from the generator having a tubular needle extending therefrom,

and means for supporting said vessel in said compartment in position above said container with the needle extending downward from said vessel, with the lower end of the needle engaging the stopper of said container, and with the vessel and container adapted for relative vertical movement to cause the needle to pierce the stopper for suction of the eluate from the vessel into the container.

4. Apparatus as set forth in claim 3 wherein said containerization unit has an open-topped receptacle for holding said container, said supporting means extending upward from said receptacle and being detachably secured thereto.

5. Apparatus as set forth in claim 3 wherein said containerization unit has a cup for holding said container, said vessel being an elongate cylindric vessel having said needle extending down from its lower end, said supporting means comprising a tubular housing extending upward from said cup and having a detachable connection at its lower end with said cap, said vessel being slidable in said housing.

6. Apparatus as set forth in claim 3 wherein said vessel has a submicron filter for filtering bacteria and solids from the eluate.

7. Apparatus as set forth in claim 3 wherein said containerization unit has a cup for holding said container and a shield for said container, said vessel being a syringe barrel having a filter holder applied to its tip, said holder having a submicron filter therein, the needle extending from said filter holder, said supporting means comprising a tubular housing extending upward from said cup and having a detachable connection at its lower end with said cup, an annular guide removably mounted on the upper end of said housing in concentric relation therewith, said barrel extending slidably through said guide.

8. A containerization unit for containerizing the eluate containing a solution of a daughter radioisotope generated from a parent radiosotope in an evacuated container having a stopper at its upper end adapted to be pierced by a needle comprising a vessel for receiving the eluate having a tubular needle extending therefrom, and means for supporting said vessel in position above the container with the needle extending downward from said vessel, with the lower end of the needle engaging said stopper, and with the vessel and container adapted for relative vertical movement to cause the needle to pierce the stopper for suction of eluate from the vessel into the container.

9'. A containerization unit as set forth in claim 8 having an open-topped receptacle for holding said container, said supporting means extending upward from said receptacle and being detachably secured thereto.

10. A containerization unit as set forth in claim 8 having a cup for holding said container, said vessel being an elongate cylindric vessel having said needle extending down from its lower end, said supporting means comprising a tubular housing extending upward from said cup and having a detachable connection at its lower end with said cup, said vessel being slidable in said housing.

11. A containerization unit as set forth in claim 8 wherein said vessel has a submicron filter for filtering bacteria and solids from the eluate.

12. A containerization unit as set forth in claim 8 having a cup for holding said container and a shield for said container, said vessel being a syringe barrel having a filter holder applied to its tip, said holder having a submicron filter therein, the needle extending from said filter holder, said supporting means comprising a tubular housing extending upward from said cup and having a detachable connection at its lower end with said cup, an annular guide removably mounted on the upper end of said housing in concentric relation therewith, said barrel extending slidably through said guide.

13. A shield for reception of a generator for elution of a daughter radioisotope from a parent radioisotope and for reception of a containerization unit for the eluate,

said shield being made of a dense shielding material bonded to a structurally rigid material and comprising a base, a housing on the base having a relatively thin-Walled lower section defining a compartment for reception of the containerization unit, a door for insertion of said unit in said compartment and removal of said unit from said compartment, said housing having a relatively thickwalled upper section formed to provide a chamber extending down from the top of said upper section for receiving the generator, the lower end of said chamber opening into said compartment for drainage of eluate from the generator into said unit, and a lead closure for the upper end of said chamber.

14. A shield as set forth in claim 13 having a seat at the lower end of said chamber for the lower end of the generator and an annular recess around the upper end of said chamber for seating the closure.

15. A shield as set forth in claim 13 wherein the dense shielding material is lead and the structurally rigid material is steel.

References Cited UNITED STATES PATENTS l/l96l Shapiro et al. 2/ 1968 Bruno et al.

ARCHIE R. BORCI-IELT, Primary Examiner. 

